Our long-term research objective is the study of mitral regurgitation. The factors which determine the regurgitant flow in mitral insufficiency are the systolic pressure gradient between the left ventricle and atrium, the duration of the regurgitation, and the regurgitant orific area. In previous studies we have established that the effective regurgitant area is not a fixed quantity. Our working hypothesis is that ventricular volume is a significant determinant of the regurgitant area and hence of the amount of regurgitation. This proposal is designed to test that hypothesis by studying the dynamics of acute mitral regurgitation; by defining the factors which influence the effective regurgitant area; and by determining whether they do so independently of ventricular volume changes. In open-chest dogs, phasic transmitral flow (forward and regurgitant) will be measured along with other dynamic parameters: aortic flow, left ventricular pressure, dp/dt, left atrial pressure, ECG and ventricular dimensions (echographic and ultrasonic). These measurements along with ejection fraction and ventricular volume (thermodilution) will allow us, on a beat-to-beat basis, to quantify the dynamics of regurgitation; to determine the factors influencing regurgitation; and to characterize the state of cardiac function. The dynamics of acute mitral regurgitation will be studied under conditions of both normal and compromised ventricular function including: volume loading, enhanced and depressed myocardial contractility, vasodilator therapy, changes in systemic pressure, global myocardial depression, regional myocardial dysfunction, and combinations of these conditions. Defining the mechanisms operating in acute mitral regurgitation under differing dynamic conditions should be of clinical value and help us to identify patients in whom medical therapy will be of value or in whom surgery is the treatment of choice.